The Journal of Neurophysiology Vol. 77 No. 5 May 1997, pp. 2717-2722
Copyright ©1997 The American Physiological Society

Effects of Anions on ATP-Activated Nonselective Cation Current in NG108-15 Cells

Hiromi Kaiho, Junko Kimura, Isao Matsuoka, and Hironori Nakanishi

Department of Pharmacology, Fukushima Medical College, Fukushima 960-12, Japan

Kaiho, Hiromi, Junko Kimura, Isao Matsuoka, and Hironori Nakanishi. Effects of anions on ATP-activated nonselective cation current in NG108-15 cells. J. Neurophysiol. 77: 2717-2722, 1997. Extracellular ATP induces a nonselective cation current and elevates intracellular Ca²⁺ concentration via P_2Z receptors in NG108-15 cells. We found that the ATP-induced nonselective cation current became larger in methanesulfonic acid (MS) than in Cl external solution. We therefore examined the effects of various external anions on the ATP-induced cation current with the use of the whole cell patch-clamp technique. The concentration-response curves for ATP were obtained in different anionic external solutions. The maximum current density (I_max) and the concentration of agonist that gives 50% of maximum response (EC₅₀) value of ATP were obtained by fitting the curves with the use of the Hill coefficient of 2. The apparent I_max decreased in the order of aspartic acid (Asp) > MS > F > Cl > Br  I. The apparent EC₅₀ values for ATP were shifted to the right in the sequence of Asp < F < MS < Br < Cl < I. Thus both I_max and EC₅₀ values were affected by anions, indicating that anions are mixed-type inhibitors of the ATP-induced current. The shift of the EC₅₀ values of ATP indicates that anions interfere with ATP binding to the receptor. External Cl was a noncompetitive inhibitor with respect to external Na⁺, a major cation carrying the ATP-induced current. We conclude that extracellular anions inhibit the ATP-induced nonselective cation current at least partly by interfering with ATP binding to the P_2Z receptor, which is associated with the nonselective cation channels.

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